ABSTRACT
Histamine modulates immunity by binding to histamine receptor 2 (H2R). Cimetidine, an H2R antagonist that inhibits gastric acid secretion and treats gastrointestinal ulcers, interferes with histamine-mediated immunomodulation and may have anticancer activity. This study examined cimetidine's effect on the anticancer effect of anti-PD-L1 in colon cancer. The MTT assay, colony formation assay, and DNA histograms assessed cell viability, clonogenicity, and cell cycle distribution, respectively. Flow cytometry measured H2R and PD-L1 expression and estimated specific immune cell lineages. For the in vivo study, tumor cells were subcutaneously implanted into the right flank of BALB/c mice. Cimetidine had no significant effect on CT26 cell viability, clonogenicity, or cell cycle distribution. It also did not affect H2R and PD-L1 expression levels in CT26 cells. In vivo, anti-PD-1 and anti-PD-L1 suppressed CT26 tumor growth, whereas cimetidine showed mild antitumor activity. In the combined experiment, cimetidine significantly attenuated anti-PD-1 and anti-PD-L1' antitumor effects without major toxicity. In the tumor microenvironment, anti-PD-L1 increased CD3+ T, CD4+ T, and CD8+ T cells and M1 macrophages. Combined treatment with cimetidine reversed this. Cimetidine also reversed anti-PD-1 and anti-PD-L1's decrease in circulating and tumor-associated neutrophils. Cimetidine attenuated anti-PD-L1's antitumor effect and modulated the tumor microenvironment in colon cancer.
ABSTRACT
BACKGROUND: Massive acetabular bone defects reconstructed with allografting and antiprotrusio cage in revision hip arthroplasty is less reported in the literature. We here report a series of 84 antiprotrusio cages and analyze the risk factors associated with failure. METHODS: All instances of use of an antiprotrusio cage for massive acetabular defect (Paprosky type IIc, III, and pelvic discontinuity) between 2002 and 2017 in the authors' institute were reviewed after institutional review board's approval. Survival analyses based on clinical data, bone defect (Paprosky system), type of allograft, size of cage, fixation quality, and position of cage were performed. Failure was defined as cage loosening or breakage, poor hip function, or cage revision for any reason. RESULTS: A total of 84 cages in 77 patients (mean age, 62.9 years), with a mean follow-up period of 6.2 years, had a survival rate of 82.1%. Failure was noted in 15 hips, including mechanical failure in 8 hips, recurrent dislocation in 1 hip, poor hip function in 1 hip, and periprosthetic joint infection in 5 hips. Pelvic discontinuity, reconstruction with morselized allograft alone, and fewer than 4 fixation points to the host bone were associated with higher failure rates (hazard ratios, 4.02, 3.42, and 9.9, respectively). CONCLUSION: We found that an antiprotrusio cage combined with strut allografts, fixed securely to the host bone (>4 fixation points), are beneficial for the management of massive acetabular bone defects. However, pelvic discontinuity remains a challenge that warrants the further study of technical or prosthetic innovations, such as triï¬ange implants, cup cage, and 3D-printed implants.
Subject(s)
Arthroplasty, Replacement, Hip , Hip Prosthesis , Acetabulum/surgery , Arthroplasty, Replacement, Hip/adverse effects , Follow-Up Studies , Hip Prosthesis/adverse effects , Humans , Middle Aged , Prosthesis Failure , Reoperation , Retrospective Studies , Survival Analysis , Transplantation, HomologousABSTRACT
The association between regional economic status and the probability of renal recovery among patients with dialysis-requiring AKI (AKI-D) is unknown. The nationwide prospective multicenter study enrolled critically ill adult patients with AKI-D in four sampled months (October 2014, along with January, April, and July 2015) in Taiwan. The regional economic status was defined by annual disposable income per capita (ADIPC) of the cities the hospitals located. Among the 1,322 enrolled patients (67.1 ± 15.5 years, 36.2% female), 833 patients (63.1%) died, and 306 (23.1%) experienced renal recovery within 90 days following discharge. We categorized all patients into high (n = 992) and low economic status groups (n = 330) by the best cut-point of ADIPC determined by the generalized additive model plot. By using the Fine and Gray competing risk regression model with mortality as a competing risk factor, we found that the independent association between regional economic status and renal recovery persisted from model 1 (no adjustment), model 2 (adjustment to basic variables), to model 3 (adjustment to basic and clinical variables; subdistribution hazard ratio, 1.422; 95% confidence interval, 1.022-1.977; p = 0.037). In conclusion, high regional economic status was an independent factor for renal recovery among critically ill patients with AKI-D.
Subject(s)
Acute Kidney Injury/economics , Critical Illness/economics , Economic Status , Hospital Mortality/trends , Recovery of Function , Renal Dialysis/economics , Acute Kidney Injury/epidemiology , Acute Kidney Injury/therapy , Aged , Critical Illness/epidemiology , Critical Illness/therapy , Female , Humans , Intensive Care Units , Male , Prospective Studies , Renal Dialysis/methods , Socioeconomic Factors , Taiwan/epidemiologyABSTRACT
AIM: Acute kidney injury (AKI) carries an increasing incidence rate worldwide and increases the risk of developing end-stage renal disease (ESRD) as well as the medical expenses during the post-AKI course. The Taiwan Consortium for Acute Kidney Injury and Renal Diseases (CAKs) has thus launched a nationwide epidemiology and prognosis of dialysis-requiring acute kidney injury (NEP-AKI-D) study, which prospectively enrols critically ill patients with AKI. Through thoroughly evaluating the risk and prognostic factors of AKI, we hope to lower the incidence of AKI and ESRD from the perspective of AKI-ESRD interaction. METHODS: The CAKs includes 30 hospitals which distribute widely through the four geographical regions (north, middle, south, and east) of Taiwan, and have a 1:1 ratio of medical centres to regional hospitals in each region. The NEP-AKI-D study enrols intensive care unit-based AKI patients who receive dialysis in the four seasonal sampled months (October 2014, along with January, April, and July 2015) in the included hospitals. The collected data include demographic information, pertaining laboratory results, dialysis settings and patient outcomes. The data are uploaded in a centre website and will be audited by on-site principal investigators, computer logic gates, and the CAKs staffs. The outcomes of interest are in-hospital mortality, dialysis-dependency and readmission rate within 90 days after discharge. CONCLUSION: The NEP-AKI-D study enrols a large number of representative AKI patients throughout Taiwan. The results of the current study are expected to provide more insight into the risk and prognostic factors of AKI and further attenuated further chronic kidney disease transition.
Subject(s)
Acute Kidney Injury/epidemiology , Acute Kidney Injury/therapy , Epidemiologic Research Design , Renal Dialysis , Acute Kidney Injury/diagnosis , Acute Kidney Injury/mortality , Critical Illness , Databases, Factual , Disease Progression , Hospital Mortality , Humans , Incidence , Kidney Failure, Chronic/diagnosis , Kidney Failure, Chronic/epidemiology , Kidney Failure, Chronic/therapy , Patient Readmission , Prospective Studies , Risk Factors , Taiwan/epidemiology , Time Factors , Treatment OutcomeABSTRACT
AIM: We aimed to evaluate the impacts of heomodialysis (HD) in older patients, and potential consequences of adverse events for health insurance costs. METHODS: Two hundred and fifty-five new patients (130 were younger than 65 years and 125 were older than 65 years) who had received conventional HD for at least 1 year were reviewed. RESULTS: Older patients had significantly more arteriovenous (AV) shunt failures (0.7 ± 0.1 vs 0.4 ± 0.07, P = 0.006) and hospitalisations (0.8 ± 0.1 vs 0.4 ± 0.09, P = 0.03) than younger ones. Stepwise multivariate linear regression analysis showed that AV shunt failure was an independent risk factor for hospitalisation. CONCLUSIONS: The relatively high risk of AV shunt failures and hospitalisation in older patients highlights the additional expenditure on HD required in terms of health insurance.